Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis

Nature Medicine., 11 (8): 892- 898, 2005

Speaker : 莊旭翔                                Time : 5/10/2005, 14:00-15:00

Commentator : 黎煥耀 老師                      Place : Room 601

Abstract :

Members of suppressor of cytokine signaling (SOCS) family are potentially key negative regulators of IL-6 and INF-γsignaling. SOCS3 can attenuate proinflammatory signaling mediated by signal transducer and activator of transcription (STAT) family of proteins. After exposure to pathogenic factors such as staphylococcal enterotoxin B (SEB) and lipopolysaccharide (LPS) , or the lectin concanavalin A (ConA), host can induce acute inflammation. In this condition, authors want to know whether SOCS3 can attenuate acute inflammatory signaling. To test the hypothesis, authors developed recombinant cell-penetrating forms of SOCS3 (CP-SOCS3) to counteract SEB-, LPS- and ConA-induced acute inflammation. In animal model, intraperitoneally injected CP-SOCS3 was circulated to multiple organs and taken up by leukocytes and lymphocytes. Results indicated that CP-SOCS3 protected animals from lethal effects of SEB and LPS by suppressing the production of inflammatory cytokines and attenuating liver apoptosis and hemorrhagic necrosis. For this reason, replenishing the intracellular stores of SOCS3 suppresses cytokine-mediated signaling transduction associated with massive liver apoptosis and hemorrhagic necrosis induced by pathogen-derived agonists.

References:

1. Jo, D. et al. Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat. Med. 8, 892-898 (2005).

2. Krebs, D.L. & Hilton, D.J. SOCS proteins: negative regulators of cytokine signaling. Stem Cells 19, 378–387 (2001).